Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: Final 48-week clinical and virologic outcomes

Timothy J. Wilkin, John E. McKinnon, A. Gregory DiRienzo, Katie Mollan, Courtney V Fletcher, David M. Margolis, Barbara Bastow, Gary Thal, William Woodward, Catherine Godfrey, Ann Wiegand, Frank Maldarelli, Sarah Palmer, John M. Coffin, John W. Mellors, Susan Swindells

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background. Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)-sparing benefits, low pill burden, once-daily dosage, and safety. Methods. Subjects with virologic suppression after ≥48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks. The primary end point was time to virologic failure (confirmed HIV-1 RNA level ≥200 copies/mL). Drug resistance at virologic failure was evaluated by standard genotyping and single-genome sequencing (SGS). Residual viremia (1.1-49 copies/mL) was measured by single-copy assay. Results. Thirty-four subjects simplified to ATV/RTV alone, of whom 30 (88%) did not experience virologic failure by 48 weeks after simplification. Residual viremia did not change significantly after NRTI discontinuation among those without virologic failure but did increase 4-12 weeks before confirmed virologic failure. No major PI-resistance mutations were identified at virologic failure by standard genotyping or SGS. Conclusions. In this pilot study, simplified maintenance therapy with ATV/RTV alone maintained viral suppression in most subjects through 48 weeks. PI resistance was not detected among subjects experiencing virologic failure. Larger, randomized trials are warranted to further define the efficacy and safety of this strategy. Trial registration. ClinicalTrials.gov identifier: NCT00084019.

Original languageEnglish (US)
Pages (from-to)866-871
Number of pages6
JournalJournal of Infectious Diseases
Volume199
Issue number6
DOIs
StatePublished - Mar 15 2009

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Ritonavir
Protease Inhibitors
Reverse Transcriptase Inhibitors
Viremia
Maintenance
Nucleosides
Genome
Safety
Drug Resistance
HIV-1
Therapeutics
RNA
Mutation
Atazanavir Sulfate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy : Final 48-week clinical and virologic outcomes. / Wilkin, Timothy J.; McKinnon, John E.; DiRienzo, A. Gregory; Mollan, Katie; Fletcher, Courtney V; Margolis, David M.; Bastow, Barbara; Thal, Gary; Woodward, William; Godfrey, Catherine; Wiegand, Ann; Maldarelli, Frank; Palmer, Sarah; Coffin, John M.; Mellors, John W.; Swindells, Susan.

In: Journal of Infectious Diseases, Vol. 199, No. 6, 15.03.2009, p. 866-871.

Research output: Contribution to journalArticle

Wilkin, TJ, McKinnon, JE, DiRienzo, AG, Mollan, K, Fletcher, CV, Margolis, DM, Bastow, B, Thal, G, Woodward, W, Godfrey, C, Wiegand, A, Maldarelli, F, Palmer, S, Coffin, JM, Mellors, JW & Swindells, S 2009, 'Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: Final 48-week clinical and virologic outcomes', Journal of Infectious Diseases, vol. 199, no. 6, pp. 866-871. https://doi.org/10.1086/597119
Wilkin, Timothy J. ; McKinnon, John E. ; DiRienzo, A. Gregory ; Mollan, Katie ; Fletcher, Courtney V ; Margolis, David M. ; Bastow, Barbara ; Thal, Gary ; Woodward, William ; Godfrey, Catherine ; Wiegand, Ann ; Maldarelli, Frank ; Palmer, Sarah ; Coffin, John M. ; Mellors, John W. ; Swindells, Susan. / Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy : Final 48-week clinical and virologic outcomes. In: Journal of Infectious Diseases. 2009 ; Vol. 199, No. 6. pp. 866-871.
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abstract = "Background. Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)-sparing benefits, low pill burden, once-daily dosage, and safety. Methods. Subjects with virologic suppression after ≥48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks. The primary end point was time to virologic failure (confirmed HIV-1 RNA level ≥200 copies/mL). Drug resistance at virologic failure was evaluated by standard genotyping and single-genome sequencing (SGS). Residual viremia (1.1-49 copies/mL) was measured by single-copy assay. Results. Thirty-four subjects simplified to ATV/RTV alone, of whom 30 (88{\%}) did not experience virologic failure by 48 weeks after simplification. Residual viremia did not change significantly after NRTI discontinuation among those without virologic failure but did increase 4-12 weeks before confirmed virologic failure. No major PI-resistance mutations were identified at virologic failure by standard genotyping or SGS. Conclusions. In this pilot study, simplified maintenance therapy with ATV/RTV alone maintained viral suppression in most subjects through 48 weeks. PI resistance was not detected among subjects experiencing virologic failure. Larger, randomized trials are warranted to further define the efficacy and safety of this strategy. Trial registration. ClinicalTrials.gov identifier: NCT00084019.",
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T1 - Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy

T2 - Final 48-week clinical and virologic outcomes

AU - Wilkin, Timothy J.

AU - McKinnon, John E.

AU - DiRienzo, A. Gregory

AU - Mollan, Katie

AU - Fletcher, Courtney V

AU - Margolis, David M.

AU - Bastow, Barbara

AU - Thal, Gary

AU - Woodward, William

AU - Godfrey, Catherine

AU - Wiegand, Ann

AU - Maldarelli, Frank

AU - Palmer, Sarah

AU - Coffin, John M.

AU - Mellors, John W.

AU - Swindells, Susan

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N2 - Background. Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)-sparing benefits, low pill burden, once-daily dosage, and safety. Methods. Subjects with virologic suppression after ≥48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks. The primary end point was time to virologic failure (confirmed HIV-1 RNA level ≥200 copies/mL). Drug resistance at virologic failure was evaluated by standard genotyping and single-genome sequencing (SGS). Residual viremia (1.1-49 copies/mL) was measured by single-copy assay. Results. Thirty-four subjects simplified to ATV/RTV alone, of whom 30 (88%) did not experience virologic failure by 48 weeks after simplification. Residual viremia did not change significantly after NRTI discontinuation among those without virologic failure but did increase 4-12 weeks before confirmed virologic failure. No major PI-resistance mutations were identified at virologic failure by standard genotyping or SGS. Conclusions. In this pilot study, simplified maintenance therapy with ATV/RTV alone maintained viral suppression in most subjects through 48 weeks. PI resistance was not detected among subjects experiencing virologic failure. Larger, randomized trials are warranted to further define the efficacy and safety of this strategy. Trial registration. ClinicalTrials.gov identifier: NCT00084019.

AB - Background. Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)-sparing benefits, low pill burden, once-daily dosage, and safety. Methods. Subjects with virologic suppression after ≥48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks. The primary end point was time to virologic failure (confirmed HIV-1 RNA level ≥200 copies/mL). Drug resistance at virologic failure was evaluated by standard genotyping and single-genome sequencing (SGS). Residual viremia (1.1-49 copies/mL) was measured by single-copy assay. Results. Thirty-four subjects simplified to ATV/RTV alone, of whom 30 (88%) did not experience virologic failure by 48 weeks after simplification. Residual viremia did not change significantly after NRTI discontinuation among those without virologic failure but did increase 4-12 weeks before confirmed virologic failure. No major PI-resistance mutations were identified at virologic failure by standard genotyping or SGS. Conclusions. In this pilot study, simplified maintenance therapy with ATV/RTV alone maintained viral suppression in most subjects through 48 weeks. PI resistance was not detected among subjects experiencing virologic failure. Larger, randomized trials are warranted to further define the efficacy and safety of this strategy. Trial registration. ClinicalTrials.gov identifier: NCT00084019.

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